Innostellar Biotherapeutics: Clinical Needs Drive Founding Vision, Ophthalmic Gene Therapy IND Advanced Within Two Years

On May 9, the "Implementation Regulations of the Pharmaceutical Administration Law of the People's Republic of China (Revised Draft for Public Comment)" (hereinafter referred to as the draft for comment) issued by the National Medical Products Administration introduced and revised several provisions related to drugs for rare diseases. The most noteworthy point is that the draft for comment proposed,For newly approved orphan drugs, a market exclusivity period of up to 7 years will be granted, provided that the marketing authorization holder commits to ensuring drug supply, and during this period, no identical products will be approved for marketing.

The extension of market exclusivity for new orphan drugs is undoubtedly a policy boon for many companies in China that are developing potential first-in-class drugs in the rare disease field. Innostellar Biotherapeutics Co., Ltd. is one of them.

Recently, LX101 Injection, a product of Shanghai Langsheng Biotechnology (under Innostellar Biotherapeutics), completed the first subject dosing in its Phase I clinical trial.By carrying the normal RPE65 gene through adeno-associated virus 2 (AAV2), LX101 can specifically recognize and transfect diseased retinal pigment epithelial cells, and continuously express the RPE65 protein that patients lack, restoring normal visual cycling to achieve the therapeutic goal of improving visual function. As the first drug in China approved to conduct clinical trials for LCA gene therapy, the smooth progress of LX101 injection in clinical applications indicates a significant step forward in bringing technological breakthroughs for treating rare ophthalmic diseases closer to clinical use in China.

Successfully advancing the first self-developed product to clinical trials within two years also demonstrates the execution capability of the Innostellar Biotherapeutics team. VCBeat learned that LX101 injection is not only the first drug in China approved to conduct clinical trials for gene therapy targeting inherited retinal diseases, but the early clinical research on LX101 injection also represents the first investigator-initiated gene therapy clinical study for IRD in China.

What kind of team is Innostellar Biotherapeutics? What is the background and strength of the team members that allows them to quickly initiate clinical trials and advance product development so rapidly? VCBeat spoke withDr. Fenghua Wang, Founder & CEO of Innostellar BiotherapeuticsA conversation was conducted.

"Although retinal degeneration appears to be a single disease, there are as many as two or three hundred gene mutations that can cause it, and the pathogenic mechanisms triggered by each mutation are different. If we don't understand what type of disease-causing mutation the gene under study represents and how this mutation influences the onset and progression of the disease, it could lead to the failure of product development," Dr. Wang Fenghua told VCBeat. A deep understanding of diseases and clinical needs forms the foundation of Innostellar Biotherapeutics' research and development.

As the director of the Shanghai Ophthalmic Engineering Technology Research Center,Before founding Innostellar Biotherapeutics, Dr. Wang Fenghua's clinical team had already conducted extensive clinical research on IRD.After witnessing the remarkable clinical efficacy of gene therapy in treatment, she was determined to translate translational medicine and clinical research into products, which is a natural extension.

The research experience accumulated in the early stages undoubtedly laid a solid foundation for Innostellar Biotherapeutics' subsequent clinical trials. In addition,Dr. Wang Fenghua's years of accumulated clinical experience in the ophthalmology field is an important reason for the team’s ability to quickly and smoothly carry out clinical research.

"For clinical trials initiated by investigators, the primary responsibility lies with the investigators. Therefore, during the conduct of clinical trials, investigators must ensure the quality of the products used in clinical research and maintain full communication with the ethics committee throughout the trial to address all concerns the ethics committee may have regarding the clinical trial."

With years of clinical experience, Innostellar Biotherapeutics' clinical team highly focuses on the rights and interests protection of patients enrolled in clinical trials, minimizing the risks that patients may face. Meanwhile, they are well-versed in various GCP regulations involved in ophthalmology clinical trials. Additionally, as clinical physicians with extensive frontline experience,The resources and influence accumulated at hospitals and among patients have enabled Innostellar Biotherapeutics to excel in the clinical recruitment of rare disease patients.These are important reasons why Innostellar Biotherapeutics can quickly, standardly, and smoothly carry out relevant clinical trials.

Efficient clinical advancement is one aspect; the ability to successfully apply for clinical trials relies on the scaled production and quality research of the product, aiming to achieve the goal of "safe, effective, and controllable quality." This would not be possible without another founder of the Innostellar team.Dr. Guiyi Zhang, Co-founder and CTO of Innostellar BiotherapeuticsDr. Zhang is reportedly an industrialization expert in the field of gene therapy, with extensive experience in the development, large-scale production, and quality research of gene therapy products.

Dr. Zhang Guiyi has 25 years of experience in process development and GMP manufacturing at U.S. biopharmaceutical companies and is a CMC expert in large-molecule biologics and viral vectors for gene therapy. After accumulating extensive CMC experience with recombinant proteins and monoclonal antibody innovative drugs, Dr. Zhang has been leading the process development and GMP production of viral products (mainly viral vectors for vaccines and gene therapy) since 2011. From 2015 to 2020, Dr. Zhang served as Director of Process Development at REGENXBIO Inc., where she developed manufacturing processes for six AAV products, including ophthalmic gene therapy product RGX314. She is the first author of two U.S. patents related to the manufacturing processes of AAV products.

The two founders share a common trait—a strong sense of mission. “Developing gene therapies that are affordable for the average Chinese citizen, and restarting the healthy lives of patients with genetic and chronic diseases” is their shared mission and vision. “Addressing unmet clinical needs” is their common goal. Additionally, both are highly pragmatic in their personalities and prefer to “speak less and do more.” Their shared sense of mission, aligned objectives, and similar personalities have fostered an unspoken默契 in their work. This unity of purpose, combined with the courage and ability to overcome any obstacles, has solidified into the team’s strong execution capabilities.

With specialized expertise in their respective professional backgrounds and fields, the founders have successfully achieved complementary strengths. Dr. Wang has深耕多年 in the ophthalmology field and possesses profound insights into the pathological mechanisms of various retinal diseases, allowing her to focus more on early product design that meets clinical needs during product development. Meanwhile, Dr. Zhang brings extensive experience accumulated over the years in the innovative biologics industry in North America. She is highly skilled in process development, quality research, and large-scale production of AAV products. Due to their mutual respect for each other's capabilities and accomplishments in their respective domains, Dr. Wang and Dr. Zhang collaborate seamlessly, discussing all matters with perfect coordination. Since its establishment, the company has made smooth progress in both operational development and pipeline advancement.

Interestingly, the friendship between the two founders of Innostellar Biotherapeutics began with an amusing story of "meeting in person after being online friends." "We were introduced by a friend from the U.S. and initially became 'online friends.' All our subsequent meetings and discussions happened online," said Dr. Wang. Due to their shared mission, vision, values, complementary expertise, and compatible personalities, Wang and Zhang eventually evolved from friends into business partners.

In March 2020, Zhang Bo resolutely joined Innostellar Biotherapeutics. Afterwards, during the global pandemic, she returned to China with her family and wholeheartedly devoted herself to entrepreneurship alongside Wang Bo.

In 2021, when VCBeat's New Medicine first interviewed Dr. Wang, she was still troubled by how to recruit more suitable talents. At that time, she said, "The biggest problem we are facing now is recruitment. The talents in the CGT field are extremely sought-after."

Since the CGT field is still in its early stages of development, talent is already scarce, and it is very challenging for startups to recruit suitable and excellent personnel.

However, in less than a year, when Dr. Wang was recently asked about the issue of team talent building, she already had a satisfied smile on her face. "The Innostellar Biotherapeutics team is now more complete. Although industry talent is still scarce, Innostellar Biotherapeutics has been fortunate. After two years, from product development, process, production, quality, registration, operations to clinical development across the entire chain, each department has gathered a group of like-minded partners."

The team is Innostellar Biotherapeutics' second trump card, capable of rapidly and smoothly advancing products from development to clinical trials.

Dr. Wang has his own set of "talent identification" strategies. "Competence is the top priority. First, I focus on the professional background of the individual. Secondly, I hope that the realization of their personal values aligns with and promotes the realization of the company’s values, maximizing both personal and corporate value. What a startup needs is that fighting spirit—always ready to take on tough challenges."

The company's HR evaluation of Dr. Wang is that she has high emotional intelligence, greatly values talent, and is bold in utilizing people. When recruiting, she focuses more on a candidate’s practical technical and knowledge-based capabilities rather than their background or credentials, reflecting an innovative and daring mindset. Perhaps due to her rigorous medical training, Dr. Wang inherently carries a pragmatic spirit.

A Talent-Valuing Boss and a Hardworking Team: The Cohesive Force Behind Innostellar Biotherapeutics' Rapid Growth

When asked why she initially transitioned from being a clinician to becoming an entrepreneur researching gene therapy products, Dr. Wang spoke about the profound impact gene therapy had on her: "When I saw patients with eye diseases that are extremely difficult to treat through surgery regain some vision—within about a week of receiving gene therapy treatment—the excitement was indescribable."

Dr. Wang stated that for these patients, gene therapy, as an emerging technical approach, could be said to be the key to unlocking their second new life. A successful product can reach a larger patient population, and this coverage far exceeds the number of patients a doctor can treat due to limitations of time, energy, and region.

The initial intention of Innostellar Biotherapeutics' establishment was to deliver the key to "initiating a patient's second life" into the hands of every patient in need. However, the high cost of treatment has deterred most patients who wish to undergo gene therapy.

The decision to build production capacity in-house reflects Innostellar Biotherapeutics' aspiration to reduce the cost and price of gene therapy products from the source."Holding the production rights of the product in our own hands not only allows for more thorough research and control over quality but also makes it possible to manage production costs. 'To enhance the accessibility of product pricing, our CMC team is actively exploring cost-effective domestically produced alternatives, including some hardware facilities, core reagent raw materials, and more. Innostellar Biotherapeutics has a relatively open attitude towards domestically produced products.' However, Dr. Wang emphasized, 'All these choices must be based on the premise of ensuring product quality. For Innostellar, the safety and efficacy of the product will always come first.'"

In early 2021, Innostellar Biotherapeutics built a nearly 5,000-square-meter R&D and production base, which officially began operations in May 2021.In October 2021, the production and release testing of 200L AAV scale products were successfully completed. Innostellar Biotherapeutics' second product, including samples required for IIT research, has achieved self-production. The industrialization team of Innostellar has successfully scaled up the 500L AAV production process and possesses a serum-free suspension culture process platform that is currently leading internationally. "Although the investment in self-built capacity is substantial, it indeed enables faster speed and higher quality in product manufacturing."

In addition to LX101, Innostellar Biotherapeutics has also laid out several other gene therapy products in the ophthalmology field, including globally innovative targets. Dr. Wang stated,"We hope that in the next three years, we can advance approximately 7 to 8 products into the clinical trial stage for global development."